Primary objective: study the association of circulating iNKT cell numbers and function with early atherogenesis, as measured by cardiovascular magnetic resonance imaging (MRI). Secondary objectives: a) study the association of circulating iNKT cell…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Autoimmune disorders
- Appetite and general nutritional disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
iNKT cell numbers and function: numbers will be quantified by flow cytometry,
function will be quantified by in vitro stimulation with iNKT cell ligands
followed by quantitative PCR of iNKT cell cytokines.
Early atherosclerosis: measured by cardiovascular magnetic resonance imaging
(MRI), using aortic wall thickness and volume as the main readout.
Secondary outcome
Secondary study parameters/endpoints
1) Markers of systemic inflammation:
* multiplex immuno assay profiling of circulating inflammatory markers
including cytokines and adipokines will be used to quantify circulating
inflammatory mediators
* phenotyping of circulating immune cell subtypes will be used to quantify
circulating inflammatory cells
2) Cardiac ultrasonography markers for vascular dysfunction:
* screening cardiac ultrasonography including left atrial volume and left
ventricular volume and function
* intima-media thickness measurement
3) Pulse wave velocity measurement for vascular dysfunction
Other study parameters:
1) Anthropomorphic measurements: weight, length, BMI-SD, waist-hip ratio, fat
percentage (bio-impedance measurement).
2) Growth: patients and their parents will be asked for permission (signed
consent) to retrieve their growth charts from the GGD (gemeentelijke
gezondheidsdienst, CB, schoolarts).
3) Nutrition: patients will be asked to complete a nutritional diary for 3
days, which takes 10 minutes a day. Standardized nutritional diaries are used
for the cystic fibrosis adolescents already.
4) Medication use: descriptive data, will be derived from the patient
information systems (Hix in WKZ/UMC Utrecht).
5) Metabolic profile: fasting glucose/insulin, HbA1c, lipid profile.
6) Physical activity: patients will be asked to fill in a questionnaire. The
questionnaire is standardized and internationally published. The questionnaire
is used by the child physical activity centre of the hospital already.
Background summary
Prolonged survival of children with chronic disease often comes at the price of
early atherosclerosis. Chronic inflammation plays a primordial role in
atherogenesis, and invariant Natural Killer T (iNKT) cells seem one of the
important cellular players involved because of their activities in the vascular
wall and high circulating numbers in children.
Study objective
Primary objective: study the association of circulating iNKT cell numbers and
function with early atherogenesis, as measured by cardiovascular magnetic
resonance imaging (MRI).
Secondary objectives: a) study the association of circulating iNKT cell numbers
and function with other markers of systemic inflammation, and b) study the
association of established cardiac ultrasonography markers for vascular
dysfunction, such as left atrial volume and left ventricular volume and
function with early atherogenesis as measured by cardiovascular MRI, and c)
study the association between nutrition, growth, surrogate markers for
cardiovascular risk (including dyslipidemia, inflammatory parameters, visceral
fat mass, pulse wave velocity), and early atherogenesis as measured by
cardiovascular MRI.
Study design
Observational, cross-sectional study.
Study burden and risks
The study comprises two invasive procedures: one venous blood withdrawal and
one contrast-enhanced MRI procedure. The used contrast agent is
gadolinium-based (Gadovist), which is routinely used in pediatric patients.
Side effects of Gadovist are very rare, only 1 in 1000 to 1 in 10.000 patients
suffers from an acute and transient allergic reaction, usually an itch, nausea,
or small bumps on the skin. In extremely rare cases, treatment with
antihistamines or adrenalin is required. Futhermore, patients with known
contrast allergies or kidney failure will be excluded from the study. In
conclusion, the burden and risks of the study are considered minimal.
Lundlaan 6
Utrecht 3584EA
NL
Lundlaan 6
Utrecht 3584EA
NL
Listed location countries
Age
Inclusion criteria
General criteria for all groups:
* 12-19 years of age ;Obese adolescents:
Definition according to the international standards of the International Obesity Task Force, see Cole et al, BMJ, 2000. ;JIA adolescents:
* Polyarticular course JIA, including polyarticular JIA and extended oligoarticular JIA, rheumafactor negatieve. These patients often suffer from lifelong rheumatic disease, and are therefore at risk for early atherosclerosis.
* More than 1 year after diagnosis. In first year of disease, patients undergo multiple study procedures, causing a burden on patients. In order to reduce the general burden, this study will focus on patients after their first year of disease.
* BMI-SD < 2 (no obese children). ;Corrected aortic arch anomalies adolescents:
* Corrected aortic arch anomalies, i.e. hypoplastic aortic arch, coarctatio aortae, interrupted aortic arch. These patients are at risk for hypertension and early atherosclerosis.
* BMI-SD (standard deviation from BMI corrected for age and sex) < 2, to prevent including obese children in this group, to prevent obesity being a confounder in later analysis. ;Cystic fibrosis adolescents:
- Established cystic fibrosis, all mutations.
- BMI-SD < 2, to prevent inclusion of obese children so that obesity cannot be a confounder in later analysis. ;Corrected ASD adolescents:
* Corrected ASD.
* No other cardiac anomalies.
* BMI-SD < 2, to prevent inclusion of obese children so that obesity cannot be a confounder in later analysis.
NB. ASD correction < age 1 year has an excellent prognosis and is not associated with enhanced risk of early atherosclerosis.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
* Intoxication (smoking, drug-use)
* Acute illness (fever)
* Mental retardation
* Claustrophobia
* A history of allergic reactions to MR contrast fluids
* Implanted electronic devices (i.e. pacemaker, internal cardioverter-defibrillator, cochlear implants, nerve- and bone stimulators)
* Subjects with ferromagnetic clips in brain, eyes or lungs
* A known reduced kidney function (GFR< 60 ml/min/1.73m2)
* Pregnancy
* Subjects who do not wish to be informed about abnormal findings of the cardiovascular MRI
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL57924.041.16 |